Pseudomonas aeruginosa Eliminates Natural Killer Cells via Phagocytosis-Induced Apoptosis

PLoS Pathogens

Jeong Keun Ahn¹  Jeong Ki Min²  Jin Woong Chung²  You-Hee Cho²  Suk Ran Yoon²  Mira Jeong²  Suk Hyung Lee²  Mi Sun Kim³  Zheng-Hao Piao⁴  Jae Wha Kim⁵  Jin Chul Kim⁵  Inpyo Choi⁶  Kyoon Eon Kim⁷ 

[1] Antibody Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea;Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon, Republic of Korea;Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon, Republic of Korea;Department of Biological Science, Dong-A University, Busan, Republic of Korea;Department of Functional Genomics, University of Science and Technology, Daejeon, Republic of Korea;Department of Life Science, College of Natural Science, Sogang University, Seoul Republic of Korea;Genome Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon, Republic of Korea

关键词: NK cells;    Apoptosis;    Flow cytometry;    Metastasis;    Mouse models;    Cell staining;    Metastatic tumors;    Spleen;   

DOI  :  10.1371/journal.ppat.1000561

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Pseudomonas aeruginosa (PA) is an opportunistic pathogen that causes the relapse of illness in immunocompromised patients, leading to prolonged hospitalization, increased medical expense, and death. In this report, we show that PA invades natural killer (NK) cells and induces phagocytosis-induced cell death (PICD) of lymphocytes. In vivo tumor metastasis was augmented by PA infection, with a significant reduction in NK cell number. Adoptive transfer of NK cells mitigated PA-induced metastasis. Internalization of PA into NK cells was observed by transmission electron microscopy. In addition, PA invaded NK cells via phosphoinositide 3-kinase (PI3K) activation, and the phagocytic event led to caspase 9-dependent apoptosis of NK cells. PA-mediated NK cell apoptosis was dependent on activation of mitogen-activated protein (MAP) kinase and the generation of reactive oxygen species (ROS). These data suggest that the phagocytosis of PA by NK cells is a critical event that affects the relapse of diseases in immunocompromised patients, such as those with cancer, and provides important insights into the interactions between PA and NK cells.

【 授权许可】

CC BY